This invention is directed to an improved process for preparing 5-sec-alkyl-m-cresol. The process of this invention yields 5-sec-alkyl-m-cresol in higher yields and at a more economic cost than the present methods. The method comprises alkylating m-cresol with an alkene in the presence of a catalyst. The alkylated m-cresol mixture is then isomerized over the same catalyst to give a reaction mixture having a high concentration of 5-sec-alkyl-m-cresol and low concentrations of the other alkylated-m-cresols. The 5-sec-alkyl-m-cresol is recovered from the reaction product by fractional distillation and the other alkylated-m-cresols may be recycled.
This invention is particularly directed to an improved process for preparing 5-isopropyl-m-cresol (m-thymol). The invention yields m-thymol in higher yields and at a more economic cost than the present methods. The method comprises alkylating-m-cresol with propylene in the presence of a catalyst. The isoproplated m-cresol mixture is then isomerized over the same catalyst to give a reaction mixture having a high concentration of m-thymol and low concentrations of the other thymol isomers. The m-thymol is recovered by fractional distillation.
This invention is also directed to the composition of matter of 5-cyclohexyl-m-cresol and 5-.alpha.-methylbenzyl-m-cresol.
The compound 5-isopropyl-m-cresol is an extremely useful intermediate for preparing insecticides. It was postulated at a symposium on "Carbamate Insecticides" at the 148th ACS meeting in the fall of 1964 that the order of insecticidal activity of alkyl phenyl N-methyl carbamate was m-alkyl&gt;&gt; o-alkyl or p-alkyl, sec-alkyl&gt;tert-alkyl&gt;&gt;n-alkyl and 4-carbon side chain&gt; 3 or 5 carbon&gt; &gt; fewer or more carbons. Therefore the N-methyl carbamate of 5-isopropyl-m-cresol would be a very effective insecticide. In fact, the N-methylcarbamate of this compound has been patented for this use. See Jaeger and Peissker, German Pat. No. 1,147,438. In addition, the 5-isopropyl-m-cresol and other 5-sec-alkyl-m-cresols are valuable intermediates for preparing other compounds. It should be noted that 5-isopropyl-m-cresol is commonly referred to in the literature by several other names. In addition to 5-isopropyl-m-cresol the compound has been referred to as 3-isopropyl-5-methylphenol, symmethrical thymol (sym-thymol), 5-thymol, or m-thymol. These terms have been and may be used interchangeably for referring to the subject compound.
Although-m-thymol and other 5-sec-alkyl-m-cresols are very useful compounds, they have not heretofore found wide commercial application. The main reason for this lack of commercialization is that before the invention herein there was no efficient and economical method for preparing 5-sec-alkyl-m-cresol particularly m-thymol. The process of the present invention is the best process considering ease of operation, cost of raw materials, disposal of by-products, recycling of isomers and unreacted starting materials and prevention of the formation of polyalkylated-m-cresols.
The compound 5-isopropyl-m-cresol has been known for many years. It was first synthesized by E. Knoevenagel in 1894 under the same symmetrical carvacrol. Knoevenagel brominated m-camphor forming the unstable dibromide which began to lose hydrogen bromide at room temperature. On heating, all the bromine was removed as HBr leaving s-carvacrol. The first indication that m-thymol was formed in the condensation of propylene with m-cresol over sulfuric acid was reported by Howard and Blagden in British Pat. No. 214,866, but the compound was not characterized. The reaction of m-cresol with isopropyl chloride using aluminum chloride as the catalyst is the subject of U.S. Pat. No. 2,064,885. According to the patent, thymol is the major product below -10.degree. C. with a little m-thymol present. The latter is obtained almost pure if the condensation is performed at 30.degree.-60.degree. C.
Chichibabin studied the thymol isomers in greater detail Ann. de Chemie, 17,317 (1942) and gave the following physical constants:
______________________________________ Isomer Boiling Point Melting Point ______________________________________ 2 - (vic) 228.5.degree./760 mm. 69.degree. Thymol (6-) 231.8.degree./758 mm. 50.5.degree. 5-(sym) 241.degree. 51.0.degree. 4-(p-) 245-6.degree. 114.degree. ______________________________________
He performed the condensations of m-cresol with isopropyl alcohol with both phosphoric and sulfuric acid catalysts, and the condensation of-m-cresol with isopropyl chloride with an aluminum chloride catalyst. His work showed that the meta-isomer was the major product at elevated temperatures. In addition he postulated that the 5-isomer was the most stable isomer. Chichibabin expressed surprise that Smith, J. Am. Chem. Soc. 55,849, (1933), did not find m-thymol in the aluminum chloride-catalyzed isomerization of m-cresyl isopropyl ether. However, Niederl et. al; J. Am. Chem. Soc. 53,1928 (1931) and Sowa, et al, J. Am. Chem. Soc. 54,2019 (1932) also failed to isolate the symmetrical isomer of thymol.
Carpenter and Easter, J. Org. Chem. 20,401 (1955), studied the preparation of all isopropyl cresols and gave the following physical constants:
______________________________________ Oxyacetic Acid p-Nitrobenzoate Isomer M.P., .degree. C M.P., .degree. C M.P., .degree. C ______________________________________ 2-Isopropyl-3-methyl phenol (vic-thymol) 70-1 147.5-148.5 107.5-108.5 4-Isopropyl-3-methyl phenol (p-thymol) 112-3 128-9 143-4 5-Isopropyl-3-methyl phenol (sym-thymol) 50-50.5 87-8 87-8 6-Isopropyl-3-methyl phenol (thymol) 51.5 150 70 ______________________________________
They obtained the pure 5-thymol by alkylation of m-cresol and hydrolysis of its p-nitrobenzoate.
A review of the literature shows that the following methods have been used to prepare m-thymol:
1. Bromination of 3-methyl-5-isopropyl-2-cyclohexen-1-one and dehydrobromination (Knoevenagel, 1894). PA1 2. Dehydrogenation of 3-methyl-5-isopropyl-2-cyclohexen-1-one (Horning 1945, 1949). PA1 3. Sulfonation of m-cresol, condensation with propylene and hydrolysis of sulfuric acid (Howard, Blagden, 1924). PA1 4. Condensation of isopropyl chloride with m-cresol in ethylene dichloride by molar quantities of aluminum chloride (Carpenter, 1936; Chichibabin 1942 and 1955). PA1 5. Condensation of isopropyl ether with m-cresol over acid clay (Carpenter and Easter, 1955). PA1 6. From 2,6-dimethyl-4-isopropylpyrylium perchlorate and NaOH in 14% yield (Balaban and Nenitzescu). PA1 7. Hydrolysis of 5-methoxy-7-methylthionaphthene over Raney nickel followed by hydrolysis of the ether by pyridine hydrochloride (Demerseman 1963). PA1 8. Reaction of m-cresol with propylene in the presence of ZnBr.sub.2 --H.sub.2 O--HBr (Kalav 1972).
It is obvious that only a few of the above processes are capable of commercial production. Moreover, those which are capable of being used commercially are not economically feasible. For example, route 4 above requires large amounts of aluminum chloride which has to be removed. Also, isopropyl chloride instead of the much cheaper propylene is used. Route 5 is a feasible process but uses the more expensive and potentially hazardous isopropyl ether.
There is very little information available on the preparation and use of the 5-sec-alkyl-m-cresols other than m-thymol. There are a few references which teach about 5-ethyl-m-cresol and 5-t-butyl-m-cresol. In addition there are several references which disclose 5-sec-butyl-m-cresol. For example see the following references: U.S. Pat. No. 2,898,322; Journal of Chromatography 23 120 (1966) and Journal of Chromatography 23 417, (1966). I have been unable to find any reference to the composition of matter or use of other 5-sec-alkyl-m-cresols. The compounds 5-cyclohexyl-m-cresol and 5 -.alpha.-methylbenzyl-m-cresol are new compositions of matter.
Therefore, it is the object of this invention to provide a method for economically preparing 5-sec-alkyl-m-cresol particularly 5-isopropyl-m-cresol.